Metronomic chemotherapy in breast cancer

New effective therapies are under development in breast cancer; at the same time attempts are being made to modify the dosage of already available drugs. The major challenge is to treat patients with multiple comorbidities who are not candidates for standard chemotherapy. An alternative for these patients may be a metronomic chemotherapy, which is based on continuous administration of drugs at very low doses every day or in short intervals. This also cause antiangiogenic and immune-modulating effects. The tolerance of the metronomic therapy is better, which improves the patients’ quality of life. More and more data indicate the use of multidrug metronomic regimens in a broader group of breast cancer patients.This article discusses the use of metronomic chemotherapy in patients with metastatic breast cancer, highlighting the most well—established regimens, which should be considered first of all in elderly patients with comorbidities, who do not need a rapid response to therapy. Published data support also the consideration of the use of multi-drug metronomic chemotherapy in wider group of breast cancer patients. The course of research in this approach has been outlined in patients undergoing adjuvant therapy and receiving maintenance treatment in patients with triple negative breast cancer.New effective therapies are under development in breast cancer; at the same time attempts are being madeto modify the schedules of administration and doses of already available drugs. The major challenge is to treatpatients with multiple comorbidities, who are not candidates for standard chemotherapy. An alternative for thesepatients may be a metronomic chemotherapy, which is based on continuous administration of drugs at very lowdoses every day or in short intervals. This also causes antiangiogenic and immune-modulating effects. The toleranceof the metronomic therapy is better, which improves the patients’ quality of life. More and more data indicatethe use of multidrug metronomic regimens in a broader group of breast cancer patients.This article discusses the use of metronomic chemotherapy in patients with metastatic breast cancer and focuseson the best established regimens of potential use as first-line therapy in elderly patients with comorbidities, whodo not need a rapid response to therapy. Published data support also the consideration of the use of multi-drugmetronomic chemotherapy in wider group of breast cancer patients. The course of research in this approachhas been outlined in patients undergoing adjuvant therapy and receiving maintenance treatment in patients withtriple-negative breast cancer

Inhibitory kinazy 4/6 zależnej od cyklin w leczeniu zaawansowanego raka piersi z dodatnią ekspresją receptorów estrogenowych

Rak piersi jest najczęstszym nowotworem złośliwym u kobiet w Polsce i główną przyczyną zgonu w tej grupie chorych mimo istotnej poprawy w jego wczesnym rozpoznawaniu i leczeniu. W raku piersi z dodatnią ekspresją receptora estrogenowego bardzo często występuje aktywacja osi CDK4/CDK6/E2F, a jednym z mechanizmów działania terapii hormonalnych jest supresja aktywności kinaz CDK4 i CDK6. Hamowanie kinaz CDK jest ważnym celem działania nowych leków. W niniejszej pracy omówiono dwa inhibitory CDK4/6, które, jak wskazują obiecujące wyniki opublikowanych w ostatnim czasie badań, cechują się skutecznym działaniem: palbocyklib i rybocyklib. W badaniach III fazy z palbocyklibem i rybocyklibem uzyskano wyniki mające wpływ na zmianę praktyki klinicznej, ponieważ wykazały one, że dołączenie tych leków do standardowej terapii hormonalnej w ramach leczenia pierwszej linii powoduje imponującą poprawę przeżycia wolnego od progresji u chorych z ER-dodatnim, HER2-ujemnym rakiem piersi

Chemioterapia metronomiczna w raku piersi

U chorych na raka piersi poszukuje się nowych metod leczenia i podejmuje się próby modyfikacji sposobu dawkowania już dostępnych leków. Duże wyzwanie stanowi leczenie chorych ze współistniejącymi chorobami, u których istnieją ograniczone możliwości stosowania standardowej chemioterapii. Alternatywą może być chemioterapia metronomiczna, która polega na stosowaniu leku w małej dawce każdego dnia lub w krótkich odstępach. Pozwala to dodatkowo uzyskać efekt antyangiogenny i immunomodulujący. Tolerancja chemioterapii metronomicznej jest zdecydowanie lepsza, co ma korzystny wpływ na jakość życia. Niniejszy artykuł omawia doniesienia na temat zastosowania chemioterapii metronomicznej u chorych na uogólnionego raka piersi i wskazuje schematy najbardziej uzasadnione naukowo do rozważenia — przede wszystkim u chorych w starszym wieku lub ze współistniejącymi chorobami, u których nie ma konieczności uzyskania szybkiej odpowiedzi na leczenie. Dostępne wyniki badań uzasadniają również rozważenie stosowania wielolekowych schematów chemioterapii metronomicznej w szerszej grupie chorych na raka piersi. Jednocześnie w opracowaniu przedstawiono kierunki badań z zastosowaniem chemioterapii metronomicznej w leczeniu uzupełniającym oraz w postępowaniu podtrzymującym u chorych na potrójnie ujemnego raka piersi

Atezolizumab in the treatment of patients with breast cancer

Immunotherapy is a modern method of treatment which is being tested in breast cancer patients. The first approved drug in this group was atezolizumab introduced for the treatment of patients with locally advanced and inoperable or metastatic triple-negative breast cancer (TNBC) with expression of programmed death receptor type 1 (PD-L1) on immunologic cells (IC) of ≥1%, who had not received prior chemotherapy for advanced disease. The results of the registration study IMpassion130 indicated that atezolizumab improved patient outcomes when used in combination with nab-paclitaxel. This article summarizes the most important analyzes of that study. The necessity to use the validated VENTANA SP142 assay to assess PD-L1 expression, which is necessary for the qualification of patients for this therapy, was emphasized. Additionally, the available data on the first results of the studies in patients with early TNBC as well as with human epidermal receptor type 2 (HER2)-positive and estrogen receptor (ER)-positive HER2-negative cancers treated with atezolizumab are discussed

Recent advances in the treatment of triple-negative breast cancer

Triple-negative is the rarest breast cancer biological subtype of breast cancer, but has the most aggressive course. The resuls of chemotherapy, especially in advanced disease, are unsatisfactory. Numerous clinical trials have been conducted, that resulted in registrations of new drugs decreasing the risk of recurrence and improving the outcome of patients with metastatic disease. The article summarizes the data on modern therapies registered in recent years. The role of pembrolizumab in perioperative treatment in the early stage was indicated, as well as the importance of olaparib in BRCA mutation carriers. Additionally, in patients with metastatic the indication for immunotherapy (pembrolizumab and atezolizumab), sacituzumab govitecan and PARP inhibitors (olaparib and talazoparib) in BRCA mutation carriers were highlighted

Chemotherapy compliance in elderly patients with solid tumors: a real-world clinical practice data

Introduction. Malignant tumors in elderly people are more than ten times more prevalent than in the younger population. The data on the compliance with chemotherapy in older cancer patients managed outside of clinical trials is scarce.  Material and methods. We retrospectively assessed 181 consecutive cancer patients aged 65 years or more who received systemic chemotherapy. The study aimed to examine chemotherapy compliance in a large series of elderly patients managed in routine clinical practice. We also investigated the ability to complete chemotherapy in relation to selected factors, such as tumor type, treatment setting and line, type of chemotherapy, presence of comorbidities, body mass index (BMI), an expected glomerular filtration rate, hemoglobin level (Hb), a neutrophil- to-lymphocyte ratio, and Eastern Cooperative Oncology Group performance status (PS).  Results. Thirty-three percent of patients did not complete an initially pre-defined chemotherapy plan. The main reasons were disease progression (20%) and unacceptable toxicity (10%). Independent factors related to premature treatment termination included a lower BMI, a lower Hb level, lower PS, and palliative (compared to currative) setting.  Conclusions. In conclusion, premature chemotherapy termination not related to disease progression is relatively rare in elderly patients and may be predicted with routinely used clinical parameters

Breast cancer in young women

Opieka nad młodymi chorymi na raka piersi stanowi wyzwanie dla lekarzy wielu specjalności. Wprowadzanie coraz skuteczniejszej terapii skutkuje poprawą wyników leczenia. Jednocześnie jakość życia po leczeniu onkologicznym staje się coraz ważniejsza. Problemy młodych kobiet, które zachorowały na raka piersi, różnią się od tych, które dotyczą starszych pacjentek. Odnosi się to zwłaszcza do zaburzeń płodności pod wpływem leczenia systemowego. W ostatnich latach wprowadzono nowe zalecenia postępowania terapeutycznego oraz postępowania w sytuacjach specyficznych dla tej grupy wiekowej. W niniejszej pracy zaprezentowano kompleksowe podejście do opieki nad młodymi chorymi na raka piersi. Przedstawiono aktualne zasady leczenia, rekomendowane przez towarzystwa naukowe. Omówiono specyficzne sytuacje kliniczne: problem z prokreacją po chemioterapii, metody zachowania płodności, ciążę i karmienie po pierwotnym leczeniu raka piersi, raka piersi w ciąży i antykoncepcję.Caring for young breast cancer patients is a challenge for different medical specialists. An introduction of more effective agents results in improved outcomes. At the same time, the quality of life after cancer becomes more important. The problems of young women who develop breast cancer differ from those that apply for older patients. It applies especially to fertility impairment due to systemic therapy. In recent years, new guidelines for the treatment and management of young breast cancer patients in certain specific situations have been developed. The article presents the comprehensive approach to care for young breast cancer patients. The current principles of treatment, recommended by scientific societies, were discussed. The following specific clinical issues were addressed: fertility after chemotherapy, the methods of fertility preservation, pregnancy and breastfeeding after breast cancer, breast cancer in pregnant women, and contraception

PD-L1-Positive High-Grade Triple-Negative Breast Cancer Patients Respond Better to Standard Neoadjuvant Treatment-A Retrospective Study of PD-L1 Expression in Relation to Different Clinicopathological Parameters.

Triple negative breast cancer (TNBC) is typically a high-grade breast cancer with poorest clinical outcome despite available treatment modalities with chemo-, immuno- and radiotherapy. The status of tumor-infiltrating lymphocytes (TILs) is a prognostic factor closely related to programmed death ligand 1 (PD-L1) expressed on T lymphocytes modulating antitumor immunity. Immune-checkpoint inhibitors (ICI) are showing promising results in a subset of breast cancer patients in both neo- and adjuvant settings. Pathologic complete response (pCR) after neoadjuvant treatment was found to be associated with better prognosis. We analyzed the prognostic and predictive significance of PD-L1 (SP142 assay) immunohistochemical expression on TNBC patients' samples as illustrated by pCR with regard to its relation to treatment regimen, stage, BRCA mutational status and outcome. Furthermore, we analyzed a few other clinicopathological parameters such as age, TILs and proliferation index. The study highlighted a positive role of PD-L1 evaluation for personalized pCR probability assessment. Although considerable research was made on comparison of PD-L1 level in TNBC with different patient parameters, to our best knowledge, the relation of PD-L1 status to pCR while taking treatment regimen and stage into consideration was so far not investigated

Breast-conserving surgeries in HER-positive breast cancer patients are performed too rarely in Poland

Breast cancer is the most common cancer among women in Poland and worldwide; after lung cancer it is the second highest cause of death among females with malignancies. HER2 positive breast cancer occurs in ca.15–20% of all cases. More often than other subtypes, it affects younger patients and more often spreads metastasises to internal organs. The new drugs against the HER2 receptor significantly improve patients’ prognoses, regardless of the initial stage. The authors of the study involved 1503 patients with HER2 positive breast cancer from all stages (I–IV); 482 patients received preoperative systemic therapy (chemotherapy or hormonal therapy), 385 trastuzumab. Among the 1219 females qualified to surgery, 734 (60%) underwent a mastectomy, 485 (40%) had breast conserving therapy with adjuvant radiotherapy, some of them had preoperative systemic treatment